An Exploratory Study of Field Failures

Field failures, that is, failures caused by faults that escape the testing phase leading to failures in the field, are unavoidable. Improving verification and validation activities before deployment can identify and timely remove many but not all faults, and users may still experience a number of annoying problems while using their software systems. This paper investigates the nature of field failures, to understand to what extent further improving in-house verification and validation activities can reduce the number of failures in the field, and frames the need of new approaches that operate in the field. We report the results of the analysis of the bug reports of five applications belonging to three different ecosystems, propose a taxonomy of field failures, and discuss the reasons why failures belonging to the identified classes cannot be detected at design time but shall be addressed at runtime. We observe that many faults (70%) are intrinsically hard to detect at design-time

Therapeutic management of complicated talar extrusion: literature review and case report

Total extrusion of the talus with interruption of all ligaments (missing talus) is a rare injury. We describe the case of a 27-year-old man who reported total extrusion of the talus after a motorbike accident with interruption of all talar ligaments. In the first repair effort, the articular void left by the talus was filled with antibiotic cement and the wound was closed primarily. Nevertheless, the skin overlying the talar joint displayed necrosis. In order to cover the cutaneous defect, improve local vascularization, and allow reimplantation of the talus, a sural fasciocutaneous island flap was harvested. Subsequently, the original talus was placed and arthrodesis of the subtalar joint was performed. The patient was able to walk bearing full weight without support equipment after 6 months. Several therapeutic options have been suggested in such cases, including replacing the talus, tibiocalcaneal arthrodesis, and pseudoarthrodesis. The rarity and peculiarity of such cases make the establishment of generalized guidelines an arduous task, leaving the choice of treatment to the surgeon, in conformity with each case’s peculiarity. In this case use of the flap may have promoted the vascularization of the reimplanted talus, thus avoiding avascular necrosis and allowing successful reimplantation of the original talus

Surveillance and habitat diversity affect European brown hare ( Lepus europaeus ) density in protected breeding areas

AbstractThe European brown hare (Lepus europaeus) is an important game species throughout Europe. In Italy, for preventing the introduction of allochthonous strains, the management of brown hare populations has focused on the establishment of small protected areas (ZRCs), appositely managed for disposing of wild-born hares for restocking hunting territories. We investigated the effects of both land cover and surveillance on hare density and habitat preferences in 20 ZRCs, monitored twice per year (pre- and post-breeding periods) between 1997 and 2017. Density, as assessed by spotlight counts, ranged between 2.8 and 47.0 ind/km2 in spring and 5.0 and 68.4 ind/km2 in autumn. Surveillance, percent length of protected boundaries, year of institution and habitat diversity, as assessed by Shannon's Index, were the main factors affecting hare density. During their foraging activity, hares selected ryegrass, hayfields and lucerne, while avoided maize stubble and ploughed fields and were never recorded in poplar plantations or next to human settlements. While the effects of habitat heterogeneity on hare density have been widely studied, we suggest that the involvement of local stakeholders may be of paramount importance for ensuring effective conservation measures

CloudHealth: A Model-Driven Approach to Watch the Health of Cloud Services

Cloud systems are complex and large systems where services provided by different operators must coexist and eventually cooperate. In such a complex environment, controlling the health of both the whole environment and the individual services is extremely important to timely and effectively react to misbehaviours, unexpected events, and failures. Although there are solutions to monitor cloud systems at different granularity levels, how to relate the many KPIs that can be collected about the health of the system and how health information can be properly reported to operators are open questions. This paper reports the early results we achieved in the challenge of monitoring the health of cloud systems. In particular we present CloudHealth, a model-based health monitoring approach that can be used by operators to watch specific quality attributes. The CloudHealth Monitoring Model describes how to operationalize high level monitoring goals by dividing them into subgoals, deriving metrics for the subgoals, and using probes to collect the metrics. We use the CloudHealth Monitoring Model to control the probes that must be deployed on the target system, the KPIs that are dynamically collected, and the visualization of the data in dashboards.Comment: 8 pages, 2 figures, 1 tabl

Giant congenital melanocytic naevi: review of literature

giant congenital pigmented naevi is a great reconstructive challenge for the pediatric and plastic surgeons. due to the increased risk of malignant transformation in such lesions, many procedures have been used to remove giant congenital naevi like dermoabrasion, laser treatment or surgical excision combined with reconstruction through skin expansion or skin grafting; among these, only a complete excision can offer an efficacious treatment. in our centre we use the "tissue expansion" technique in order to achieve a sufficient quantity of normal skin to perform a both staged and radical excision of these giant lesions

Synthesis and Biological Evaluation of RGD and isoDGR-Monomethyl Auristatin Conjugates Targeting Integrin (V3)

This work reports the synthesis of a series of small molecule-drug conjugates containing the \u3b1V\u3b23-integrin ligand cyclo[DKP-RGD] or cyclo[DKP-isoDGR], a lysosomally cleavable Val-Ala (VA) linker or an "uncleavable" version devoid of this sequence, and monomethyl Auristatin E (MMAE) or F (MMAF) as cytotoxic agent. The conjugates were obtained via a straightforward synthetic scheme taking advantage of a copper-catalyzed azide-alkyne cycloaddition as key-step. The conjugates were tested for their binding affinity to the isolated \u3b1v\u3b23 receptor, and shown to retain nanomolar IC50 values, in the same range of the free ligands. The cytotoxic activity of the conjugates was evaluated in cell viability assays with \u3b1v\u3b23 integrin over-expressing human glioblastoma (U87) and human melanoma (M21) cells. The conjugates possess a markedly lower cytotoxic activity compared to the free drugs, which is consistent with an inefficient integrin-mediated internalization. In almost all cases the conjugates featuring isoDGR as integrin ligand exhibited higher potency than their RGD counterparts. In particular, cyclo[DKP-isoDGR]-VA-MMAE conjugate has low nanomolar IC50 values in cell viability assays with both cancer cell lines tested (U87: 11.50 \ub1 0.13 nM; M21: 6.94 \ub1 0.09 nM) and is therefore a promising candidate for in vivo experiments.This work reports the synthesis of a series of small-molecule\u2013drug conjugates containing the \u3b1 V \u3b2 3 -integrin ligand cyclo[DKP-RGD] or cyclo[DKP-isoDGR], a lysosomally cleavable Val-Ala (VA) linker or an \u201cuncleavable\u201d version devoid of this sequence, and monomethyl auristatin E (MMAE) or F (MMAF) as the cytotoxic agent. The conjugates were obtained via a straightforward synthetic scheme taking advantage of a copper-catalyzed azide\u2013alkyne cycloaddition as the key step. The conjugates were tested for their binding affinity for the isolated \u3b1 v \u3b2 3 receptor and were shown to retain nanomolar IC 50 values, in the same range as those of the free ligands. The cytotoxic activity of the conjugates was evaluated in cell viability assays with \u3b1 v \u3b2 3 integrin overexpressing human glioblastoma (U87) and human melanoma (M21) cells. The conjugates possess markedly lower cytotoxic activity than the free drugs, which is consistent with inefficient integrin-mediated internalization. In almost all cases the conjugates featuring isoDGR as integrin ligand exhibited higher potency than their RGD counterparts. In particular, the cyclo[DKP-isoDGR]-VA-MMAE conjugate has low nanomolar IC 50 values in cell viability assays with both cancer cell lines tested (U87: 11.50\ub10.13 nm; M21: 6.94\ub10.09 nm) and is therefore a promising candidate for in vivo experiments

Distally based sural fasciomusculocutaneous flap for treatment of wounds of the distal third of the leg and ankle with exposed internal hardware

Soft tissue reconstruction of the distal third of the lower limb with exposure of the internal hardware is a challenging problem with several potential complications, such as exposure of the fracture line, fracture instability and bacterial contamination. The treatment of these lesions usually consists of substitution of the internal hardware with external fixation devices and further flap coverage. We propose a different reconstructive approach, characterized by harvesting a sural fasciomusculocutaneous flap on the exposed internal hardware once a sterile ground has been obtained. Four patients were retrospectively analyzed. Soft tissue reconstruction was achieved in all cases. In one case hardware removal was necessary for complete healing. The sural fasciomusculocutaneous flap is a safe alternative to other pedicled and free flaps. Moreover, it allows direct coverage of internal fixators, thus completing the reconstruction in less time. This flap fits best to the morphology of the wound and internal hardware, leaving the main vascular trunk of the leg intact and at the same time providing a reliable vascular supply

Increased Bone Marrow Interleukin-7 (IL-7)/IL-7R Levels but Reduced IL-7 Responsiveness in HIV-Positive Patients Lacking CD4+ Gain on Antiviral Therapy

Background: The bone marrow (BM) cytokine milieu might substantially affect T-lymphocyte homeostasis in HIV-positive individuals. Interleukin-7 (IL-7) is a bone marrow-derived cytokine regulating T-cell homeostasis through a CD4+-driven feedback loop. CD4+ T-lymphopenia is associated with increased free IL-7 levels and reduced IL-7R expression/function, which are only partially reverted by highly active antiretroviral therapy (HAART). We investigated the BM production, peripheral expression and signaling (pStat5+ and Bcl-2+ CD4+/CD8+ T cells) of IL-7/IL-7Ra in 30 HAART-treated HIV-positive patients who did not experience CD4+ recovery (CD4+ #200/ml) and who had different levels of HIV viremia; these patients included 18 immunological nonresponders (INRs; HIV-RNA#50), 12 complete failures (CFs; HIV-RNA.1000), and 23 HIVseronegative subjects. Methods: We studied plasma IL-7 levels, IL-7Ra+CD4+/CD8+ T-cell proportions, IL-7Ra mRNA expression in PBMCs, spontaneous IL-7 production by BM mononuclear cells (BMMCs), and IL-7 mRNA/IL-7Ra mRNA in BMMC-derived stromal cells (SCs). We also studied T-cell responsiveness to IL-7 by measuring the proportions of pStat5+ and Bcl-2+ CD4+/CD8+ T cells. Results: Compared to HIV-seronegative controls, CFs and INRs presented elevated plasma IL-7 levels and lower IL-7Ra CD4+/CD8+ cell-surface expression and peripheral blood production, confirming the most relevant IL-7/IL-7R disruption. Interestingly, BM investigation revealed a trend of higher spontaneous IL-7 production in INRs (p = .09 vs. CFs) with a nonsignificant trend toward higher IL-7-Ra mRNA levels in BMMC-derived stromal cells. However, upon IL-7 stimulation, the proportion of pStat5+CD4+ T cells did not increase in INRs despite higher constitutive levels (p = .06); INRs also displayed lower Bcl-2+CD8+ T-cell proportions than controls (p = .04). Conclusions: Despite severe CD4+ T-lymphopenia and a disrupted IL-7/IL-7R profile in the periphery, INRs display elevated BM IL-7/IL-7Ra expression but impaired T-cell responsiveness to IL-7, suggesting the activity of a central compensatory pathway targeted to replenish the CD4+ compartment, which is nevertheless inappropriate to compensate the dysfunctional signaling through IL-7 receptor